Population based prostate cancer screening in north Mexico reveals a high prevalence of aggressive tumors in detected cases

Background: Prostate Cancer (PCa) is the second most frequent neoplasia in men worldwide. Previous reports suggest that the prevalence of PCa in Hispanic males is lower than in Africans (including communities with African ancestry) and Caucasians, but higher than in Asians. Despite these antecedents, there are few reports of open population screenings for PCa in Latin American communities. This article describes the results of three consecutive screenings in the urban population of Monterrey, Mexico. Methods: After receiving approval from our University Hospital's Internal Review Board (IRB), the screening was announced by radio, television, and press, and it was addressed to male subjects over 40 years old in general. Subjects who consented to participate were evaluated at the primary care clinics of the University Health Program at UANL, in the Metropolitan area of Monterrey. Blood samples were taken from each subject for prostate specific antigen (PSA) determination; they underwent a digital rectal examination (DRE), and were subsequently interviewed to obtain demographic and urologic data. Based on the PSA (>4.0 ng/ml) and DRE results, subjects were appointed for transrectal biopsy (TRB). Results: A total of 973 subjects were screened. Prostate biopsy was recommended to 125 men based on PSA values and DRE results, but it was performed in only 55 of them. 15 of these biopsied men were diagnosed with PCa, mostly with Gleason scores ≥ 7. Conclusion: Our results reflect a low prevalence of PCa in general, but a high occurrence of high grade lesions (Gleason ≥ 7) among patients that resulted positive for PCa. This observation remarks the importance of the PCa screening programs in our Mexican community and the need for strict follow-up campaigns

Population based prostate cancer screening in north Mexico reveals a high prevalence of aggressive tumors in detected cases

Background: Prostate Cancer (PCa) is the second most frequent neoplasia in men worldwide. Previous reports suggest that the prevalence of PCa in Hispanic males is lower than in Africans (including communities with African ancestry) and Caucasians, but higher than in Asians. Despite these antecedents, there are few reports of open population screenings for PCa in Latin American communities. This article describes the results of three consecutive screenings in the urban population of Monterrey, Mexico. Methods: After receiving approval from our University Hospital's Internal Review Board (IRB), the screening was announced by radio, television, and press, and it was addressed to male subjects over 40 years old in general. Subjects who consented to participate were evaluated at the primary care clinics of the University Health Program at UANL, in the Metropolitan area of Monterrey. Blood samples were taken from each subject for prostate specific antigen (PSA) determination; they underwent a digital rectal examination (DRE), and were subsequently interviewed to obtain demographic and urologic data. Based on the PSA (>4.0 ng/ml) and DRE results, subjects were appointed for transrectal biopsy (TRB). Results: A total of 973 subjects were screened. Prostate biopsy was recommended to 125 men based on PSA values and DRE results, but it was performed in only 55 of them. 15 of these biopsied men were diagnosed with PCa, mostly with Gleason scores ≥ 7. Conclusion: Our results reflect a low prevalence of PCa in general, but a high occurrence of high grade lesions (Gleason ≥ 7) among patients that resulted positive for PCa. This observation remarks the importance of the PCa screening programs in our Mexican community and the need for strict follow-up campaigns

Fermi LAT observations of the Geminga pulsar

We report on the \textit{Fermi}-LAT observations of the Geminga pulsar, the second brightest non-variable GeV source in the $\gamma$-ray sky and the first example of a radio-quiet $\gamma$-ray pulsar. The observations cover one year, from the launch of the $Fermi$ satellite through 2009 June 15. A data sample of over 60,000 photons enabled us to build a timing solution based solely on $\gamma$ rays. Timing analysis shows two prominent peaks, separated by $\Delta \phi$ = 0.497 $\pm$ 0.004 in phase, which narrow with increasing energy. Pulsed $\gamma$ rays are observed beyond 18 GeV, precluding emission below 2.7 stellar radii because of magnetic absorption. The phase-averaged spectrum was fitted with a power law with exponential cut-off of spectral index $\Gamma$ = (1.30 $\pm$ 0.01 $\pm$ 0.04), cut-off energy $E_{0}$ = (2.46 $\pm$ 0.04 $\pm$ 0.17) GeV and an integral photon flux above 0.1 GeV of (4.14 $\pm$ 0.02 $\pm$ 0.32) $\times$ 10$^{-6}$ cm$^{-2}$ s$^{-1}$. The first uncertainties are statistical and the second are systematic. The phase-resolved spectroscopy shows a clear evolution of the spectral parameters, with the spectral index reaching a minimum value just before the leading peak and the cut-off energy having maxima around the peaks. Phase-resolved spectroscopy reveals that pulsar emission is present at all rotational phases. The spectral shape, broad pulse profile, and maximum photon energy favor the outer magnetospheric emission scenarios.Comment: 32 pages, 12 figures, 3 tables. Accepted for publication in The Astrophysical Journal. Corresponding authors: Denis Dumora ([email protected]), Fabio Gargano ([email protected]), Massimiliano Razzano ([email protected]

Fermi Large Area Telescope Observations of the Crab Pulsar and Nebula

We report on gamma-ray observations of the Crab Pulsar and Nebula using 8 months of survey data with the Fermi Large Area Telescope (LAT). The high quality light curve obtained using the ephemeris provided by the Nancay and Jodrell Bank radio telescopes shows two main peaks stable in phase with energy. The first gamma-ray peak leads the radio main pulse by (281 \pm 12 \pm 21) mus, giving new constraints on the production site of non-thermal emission in pulsar magnetospheres. The improved sensitivity and the unprecedented statistics afforded by the LAT enable precise measurement of the Crab Pulsar spectral parameters: cut-off energy at E_c = (5.8 \pm 0.5 \pm 1.2) GeV, spectral index of Gamma = (1.97 \pm 0.02 \pm 0.06) and integral photon flux above 100 MeV of (2.09 \pm 0.03 \pm 0.18) x 10^{-6} cm^{-2} s^{-1}. The first errors represent the statistical error on the fit parameters, while the second ones are the systematic uncertainties. Pulsed gamma-ray photons are observed up to ~ 20 GeV which precludes emission near the stellar surface, below altitudes of around 4 to 5 stellar radii in phase intervals encompassing the two main peaks. The spectrum of the nebula in the energy range 100 MeV - 300 GeV is well described by the sum of two power-laws of indices Gamma_{sync} = (3.99 \pm 0.12 \pm 0.08) and Gamma_{IC} = (1.64 \pm 0.05 \pm 0.07), corresponding to the falling edge of the synchrotron and the rising edge of the inverse Compton components, respectively. This latter, which links up naturally with the spectral data points of Cherenkov experiments, is well reproduced via inverse Compton scattering from standard Magnetohydrodynamics (MHD) nebula models, and does not require any additional radiation mechanism.Comment: 17 pages, 9 figures, Accepted for publications in Astrophysical Journa

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort.

BACKGROUND: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. METHODS: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4-18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. RESULTS: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks and hospitalizations due to asthma, in comparison to the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. CONCLUSION: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent

Susceptibility of Human Lymphoid Tissue Cultured ex vivo to Xenotropic Murine Leukemia Virus-Related Virus (XMRV) Infection

BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV) was generated after a recombination event between two endogenous murine leukemia viruses during the production of a prostate cancer cell line. Although the associations of the XMRV infection with human diseases appear unlikely, the XMRV is a retrovirus of undefined pathogenic potential, able to replicate in human cells in vitro. Since recent studies using animal models for infection have yielded conflicting results, we set out an ex vivo model for XMRV infection of human tonsillar tissue to determine whether XMRV produced by 22Rv1 cells is able to replicate in human lymphoid organs. Tonsil blocks were infected and infection kinetics and its pathogenic effects were monitored RESULTS: XMRV, though restricted by APOBEC, enters and integrates into the tissue cells. The infection did not result in changes of T or B-cells, immune activation, nor inflammatory chemokines. Infectious viruses could be recovered from supernatants of infected tonsils by reinfecting DERSE XMRV indicator cell line, although these supernatants could not establish a new infection in fresh tonsil culture, indicating that in our model, the viral replication is controlled by innate antiviral restriction factors. CONCLUSIONS: Overall, the replication-competent retrovirus XMRV, present in a high number of laboratories, is able to infect human lymphoid tissue and produce infectious viruses, even though they were unable to establish a new infection in fresh tonsillar tissue. Hereby, laboratories working with cell lines producing XMRV should have knowledge and understanding of the potential biological biohazardous risks of this virus

Fermi LAT detection of pulsed gamma-rays from the Vela-like pulsars PSR J1048-5832 and PSR J2229+6114

We report the detection of gamma-ray pulsations (> 0.1 GeV) from PSR J2229+6114 and PSR J1048-5832, the latter having been detected as a low-significance pulsar by EGRET. Data in the gamma-ray band were acquired by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope, while the radio rotational ephemerides used to fold the gamma-ray light curves were obtained using the Green Bank Telescope, the Lovell telescope at Jodrell Bank, and the Parkes telescope. The two young radio pulsars, located within the error circles of the previously unidentified EGRET sources 3EG J1048-5840 and 3EG J2227+6122, present spin-down characteristics similar to the Vela pulsar. PSR J1048-5832 shows two sharp peaks at phases 0.15 \pm 0.01 and 0.57 \pm 0.01 relative to the radio pulse confirming the EGRET light curve, while PSR J2229+6114 presents a very broad peak at phase 0.49 \pm 0.01. The gamma-ray spectra above 0.1 GeV of both pulsars are fit with power laws having exponential cutoffs near 3 GeV, leading to integral photon fluxes of (2.19 \pm 0.22 \pm 0.32) x 10^{-7} cm^{-2} ^{-1} for PSR J1048-5832 and (3.77 \pm 0.22 \pm 0.44) x 10^{-7} cm^{-2} s^{-1} for PSR J2229+6114. The first uncertainty is statistical and the second is systematic. PSR J1048-5832 is one of two LAT sources which were entangled together as 3EG J1048-5840. These detections add to the growing number of young gamma-ray pulsars that make up the dominant population of GeV gamma-ray sources in the Galactic plane.Comment: 11 pages, 4 figures, 1 table. Accepted for publication in Astrophysical Journal. Contact authors: Alice K. Harding ([email protected]), Damien Parent ([email protected]), Massimiliano Razzano ([email protected]

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)